AstraZeneca's Enhertu on a Roll with Fourth Breakthrough Therapy Designation

AstraZeneca_Leon Neal/Getty Images

Leon Neal/Getty Images

AstraZeneca's candidate breast cancer therapy Enhertu now has four Breakthrough Therapy Designations from the U.S. Food and Drug Administration (FDA) after the regulator issued another BTD based on a Phase III trial presented at the European Society for Medical Oncology Congress 2021. 

The FDA granted the latest designation based on the Phase III DESTINY-Breast03 trial on adult patients diagnosed with unresectable or metastatic HER2-positive breast cancer and have received at least one more prior anti-HER2-based regimens.

Breast cancer is one of the most common types of cancer and is one of the leading causes of mortality in women worldwide. Over two million patients were diagnosed in 2020, resulting in almost 685,000 globally. One in five cases of breast cancer is classified as HER2-positive. 

The current therapy is trastuzumab and a taxane, but this still often ends with disease progression. With that said, there is a dire need for a treatment that will further delay progression and extend survival. 

Enhertu demonstrated a 72% reduction in the risk of disease progression or death. 94% of the patients who were given Enhertu were alive for one year compared to the 85.9% rate in those treated with trastuzumab emtansine (T-DM1). The objective response rate (ORR) in Enhertu patients was 79.7% versus the T-DM1 group, which logged only 34.2%. Enhertu's safety profile was also consistent with previous clinical trials, with no new safety concerns identified. 

"This is an important step in bringing Enhertu as a potential new option in earlier lines of treatment for HER2-positive metastatic breast cancer, given the urgent need to improve outcomes. This recognition by the FDA underscores the transformative possibility of Enhertu seen with the remarkable DESTINY-Breast03 results presented at ESMO just two weeks ago," said Susan Galbraith, the executive vice president for Oncology R&D at AstraZeneca, in a statement.

DESTINY-Breast-03 trial is a global head-to-head, randomized, open-label, registrational Phase III study that assesses the efficacy and safety of Enhertu versus TD-M1. The primary efficacy endpoint is a progression-free survival (PFS) based on blinded independent central review. The secondary efficacy endpoints include duration of response, objective response rate, PFS based on investigator assessment, safety, and overall survival. 

Enhertu at 5.4mg/kg is approved in Canada, Israel, Japan, the UK, the EU, and the U.S. for unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting based on the results from the DESTINY-Breast01 trial. 

Its 6.4 mg/kg dosage is also approved in the U.S., Japan, and Israel for treating adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen.

Previous Enhertu BTD's were in late-line HER2-positive metastatic breast cancer in 2017 and HER2-mutant metastatic non-small cell lung cancer (NSCLC) and HER2-positive metastatic gastric cancer in 2020

At present, Enhertu is being evaluated in a comprehensive clinical development program for safety and efficacy across several HER2-targetable cancers, including lung, gastric, breast, and colorectal cancers.

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